The objective of this program is to apply a special high resolution electron microscope to the observation of biomolecular configuration and structure. The experimental instrument that will be used in these investigations has: a complete ultra high vacuum column, a liquid He cryostat that houses the specimen, specimen stage, objective lens and intermediate lens system, a field emission electron source for high coherence illumination, and an integrating, slow scan video system for image read-out that is interfaced to a minicomputer system with tape and disks for storage and processing of the digitized image. Enhancement of resolution and signal to noise is to be achieved through high instrumental stability and image processing methods. We are particularly concerned with studying and minimizing radiation damage by keeping the specimen in an ultra high vacuum environment at liquid He temperatures. In the applications to the study of biomolecular structure, unstained periodic arrays of the biomolecular specimen will be used and exposed to minimum radiation dosages. We are also investigating the feasibility of observing nucleotides selectively stained with heavy metals for ultimate sequencing of the primary structure of polynucleotides.